College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, South Korea.
College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, South Korea; Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, South Korea.
Biomed Pharmacother. 2022 Sep;153:113406. doi: 10.1016/j.biopha.2022.113406. Epub 2022 Jul 14.
Disuse muscle atrophy is characterized by a decrease in muscle mass and strength and an increase in glycolytic muscle fiber type. Although Schisandra chinensis extract has beneficial effects on muscle atrophy induced by various conditions (e.g., dexamethasone and aging), the effect of gomisin G, a lignan component of S. chinensis, on disuse muscle atrophy is unclear. Here, we induced disuse muscle atrophy through wire immobilization of the hind legs in mice followed by the oral administration of gomisin G. The cross-sectional area and muscle strength in disuse muscle atrophic mice were increased by gomisin G; however, the total muscle mass did not increase. Gomisin G decreased the expression of muscle atrophic factors (myostatin, atrogin-1, and MuRF1) but increased the expression of protein synthesis factors (mTOR and 4E-BP1). In HO-treated C2C12 myotubes, the level of puromycin incorporation (as a marker of protein synthesis) gradually increased in a dose-dependent manner by gomisin G. Furthermore, gomisin G induced a muscle fiber switch from fast-type glycolytic fibers (type 2B) to slow-type oxidative fibers (type I, 2A) in the gastrocnemius (GA) muscle as proved a decrease in the expression of TnI-FS and an increase in the expression of TnI-SS. Gomisin G increased mitochondrial DNA content and ATP levels in the GA muscle and COX activity in HO-treated C2C12 myotubes, improving mitochondrial function. Mechanistically, mitochondrial biogenesis is regulated by gomisin G via the Sirt 1/PGC-1α signaling pathway, targeting NRF1 and TFAM. These data suggest that gomisin G has a potential therapeutic effect on disuse muscle atrophy.
废用性肌肉萎缩的特征是肌肉质量和力量下降，糖酵解肌纤维类型增加。虽然五味子提取物对各种条件（如地塞米松和衰老）引起的肌肉萎缩有有益作用，但五味子的木脂素成分五味子素 G 对废用性肌肉萎缩的影响尚不清楚。在这里，我们通过后腿的钢丝固定在小鼠中诱导废用性肌肉萎缩，然后口服五味子素 G。五味子素 G 增加了废用性肌肉萎缩小鼠的横截面积和肌肉力量；然而，总肌肉质量没有增加。五味子素 G 降低了肌肉萎缩因子（肌肉生长抑制素、Atrogin-1 和 MuRF1）的表达，但增加了蛋白质合成因子（mTOR 和 4E-BP1）的表达。在 HO 处理的 C2C12 肌管中，五味子素 G 以剂量依赖性方式逐渐增加了对 puromycin 掺入（作为蛋白质合成的标志物）的水平。此外，五味子素 G 在比目鱼肌（GA）中诱导了一种从快型糖酵解纤维（类型 2B）到慢型氧化纤维（类型 I、2A）的肌肉纤维转换，这证明了 TnI-FS 的表达降低和 TnI-SS 的表达增加。五味子素 G 增加了 GA 肌肉中的线粒体 DNA 含量和 ATP 水平以及 HO 处理的 C2C12 肌管中的 COX 活性，改善了线粒体功能。从机制上讲，线粒体生物发生受 Sirt 1/PGC-1α 信号通路调节，靶向 NRF1 和 TFAM。这些数据表明，五味子素 G 对废用性肌肉萎缩具有潜在的治疗作用。
